INCLISIRAN: A New Approach to Lowering Cholesterol

What is Inclisiran?

Inclisiran is a new medication designed to lower cholesterol levels in the blood. It's also known by other names such as KJX839, ALN-PCSSC, and Leqvio123. This drug is part of a class of medications called small interfering RNA (siRNA) drugs, which work in a unique way compared to traditional cholesterol-lowering medications like statins4.

How Does Inclisiran Work?

Inclisiran works by targeting a protein in the body called PCSK9 (proprotein convertase subtilisin kexin type 9). This protein plays a role in controlling the levels of LDL cholesterol (often called "bad" cholesterol) in your blood. By reducing the amount of PCSK9, Inclisiran helps your body remove more LDL cholesterol from the bloodstream, leading to lower overall cholesterol levels4.

What Conditions Does Inclisiran Treat?

Inclisiran is primarily used to treat conditions related to high cholesterol levels, including:

• Primary Hypercholesterolemia: This is a condition where a person has naturally high levels of cholesterol in their blood5.
• Mixed Dyslipidemia: This refers to abnormal levels of multiple types of fats (lipids) in the blood, including cholesterol and triglycerides5.
• Familial Hypercholesterolemia: This is an inherited condition that leads to very high cholesterol levels from birth. It can be heterozygous (HeFH) or homozygous (HoFH), depending on whether a person inherits the condition from one or both parents6.
• Atherosclerotic Cardiovascular Disease (ASCVD): This is a condition where plaque builds up in the arteries, increasing the risk of heart attacks and strokes13.

Inclisiran is often prescribed for patients who have tried other cholesterol-lowering medications, such as statins, but haven't achieved their target cholesterol levels1.

How is Inclisiran Administered?

Inclisiran is given as a subcutaneous injection, which means it's injected just under the skin. The typical dose is 300 mg, usually given in the following schedule123:

1. Initial dose
2. Another dose after 3 months (90 days)
3. Then every 6 months thereafter

This infrequent dosing schedule is one of the advantages of Inclisiran compared to some other cholesterol medications that need to be taken daily or weekly1.

Effectiveness of Inclisiran

Clinical trials have shown that Inclisiran can be highly effective in lowering LDL cholesterol levels. Some key findings include:

• Inclisiran can reduce LDL cholesterol by 50% or more in many patients3.
• It can help patients achieve target LDL levels of less than 70 mg/dL or even less than 55 mg/dL, which are recommended targets for high-risk patients3.
• The effects of Inclisiran appear to be long-lasting, with cholesterol reductions maintained over time with the twice-yearly dosing schedule1.

Safety and Side Effects

Inclisiran has been studied in various patient populations, including those with kidney problems, and has generally been found to be well-tolerated4. However, like all medications, it can have side effects. Common side effects may include reactions at the injection site, such as pain or redness. More research is ongoing to fully understand the long-term safety profile of Inclisiran5.

Ongoing Research

Several clinical trials are currently underway to further study Inclisiran. These studies are looking at:

• The long-term safety and effectiveness of Inclisiran in different patient populations, including adolescents with familial hypercholesterolemia6.
• How Inclisiran compares to usual care in patients who have recently had a heart attack or other acute coronary syndrome7.
• The effects of Inclisiran on the buildup of plaque in the arteries, particularly in the carotid arteries that supply blood to the brain2.
• How Inclisiran performs in real-world settings, outside of controlled clinical trials5.

These ongoing studies will help doctors and patients better understand how to use Inclisiran most effectively and safely in different situations.